Acyclovir 59277-89-3

Resistance

To date, resistance to aciclovir has not been clinically significant. Mechanisms of resistance in HSV include deficient viral thymidine kinase; and mutations to viral thymidine kinase and/or DNA polymerase, altering substrate sensitivity. Acyclovir has also shown cross-resistance with Valacyclovir and Famcyclovir.

Pharmacokinetics

Aciclovir is poorly water soluble and has poor oral bioavailability (15-30%), hence intravenous administration is necessary if high concentrations are required. When orally administered, peak plasma concentration occurs after 1–2 hours. Aciclovir has a high distribution rate, only 30% is protein-bound in plasma. The elimination half-life of aciclovir is approximately 3 hours. It is renally excreted, partly by glomerular filtration and partly by tubular secretion. The poor oral bioavailability may also be improved by administering Valaciclovir, which has an oral bioavailability of about 55%. Valaciclovir is then converted to Aciclovir by esterases via hepatic first-pass metabolism.

Clinical use

Indications

Aciclovir is indicated for the treatment of HSV and VZV infections, including:

• Genital herpes simplex (treatment and prophylaxis)
• Herpes simplex labialis
• Herpes zoster (shingles)
• Acute chickenpox in immunocompromised patients
• Herpes simplex encephalitis
• Acute mucocutaneous HSV infections in immunocompromised patients
• Herpes simplex keratitis (ocular herpes)
• Herpes simplex blepharitis (not to be mistaken with ocular herpes)
• Bell's Palsy

HIV-1 progression can be delayed by using Aciclovir, according to study lead by Dr Jairam Lingappa. Effective in 16% of cases, can delay the HAART treatment by 1–2 years. University of Washington, Seattle. During a 2 year trial, 284 people progressed with the HIV-1, versus 324 who had not been treated with Aciclovir. It has been claimed that the evidence for the effectiveness of topically applied cream for recurrent labial outbreaks is weak. An earlier review of scientific literature showed that there is some effect in reducing the number and duration of lesions if aciclovir is applied at an early stage of an outbreak. However, it was concluded that oral therapy for episodes is inappropriate for most non-immunocompromised patients based on costs and benefits, presumably in countries where aciclovir is only available on prescription. It was concluded that there is evidence for an oral prophylactic role in preventing recurrences.

Dosage forms

Aciclovir is commonly marketed as tablets (200 mg, 400 mg, 800 mg and 1 gram), topical cream (5%), intravenous injection (25 mg/mL) and ophthalmic ointment (3%). Cream preparations are used primarily for labial herpes simplex. The intravenous injection is used when high concentrations of aciclovir are required. The ophthalmic ointment preparation is only used for herpes simplex keratitis. In Singapore, it is available as a 400 mg preparation known as Avorax

.

Adverse effects

Systemic therapy

Common adverse drug reactions (≥1% of patients) associated with systemic acyclovir therapy (oral or IV) include: nausea, vomiting, diarrhea and/or headache. In high doses, hallucinations have been reported. Infrequent adverse effects (0. 1–1% of patients) include: agitation, vertigo, confusion, dizziness, oedema, arthralgia, sore throat, constipation, abdominal pain,hair loss, rash and/or weakness. Rare adverse effects (<0. 1% of patients) include: coma, seizures, neutropenia, leukopenia, crystalluria, anorexia, fatigue, hepatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis and/or anaphylaxis.

Topical therapy

Acyclovir topical cream is commonly associated (≥1% of patients) with: dry or flaking skin or transient stinging/burning sensations. Infrequent adverse effects include erythema or itch.

Detection in biological fluids

Acyclovir may be quantitated in plasma or serum in order to monitor for drug accumulation in patients with renal dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.